13-79342681-T-A

Position:

• chr13-79342681-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366735.2(RBM26):​c.2410A>T​(p.Ile804Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBM26 NM_001366735.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.04

Genes affected

RBM26 (HGNC:20327): (RNA binding motif protein 26) Enables RNA binding activity. Predicted to be involved in mRNA processing. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10876283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBM26	NM_001366735.2	c.2410A>T	p.Ile804Leu	missense_variant	17/22	ENST00000438737.3	NP_001353664.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBM26	ENST00000438737.3	c.2410A>T	p.Ile804Leu	missense_variant	17/22	5	NM_001366735.2	ENSP00000387531.2
RBM26	ENST00000438724.5	c.2338A>T	p.Ile780Leu	missense_variant	16/21	1		ENSP00000390222.1
RBM26	ENST00000267229.11	c.2329A>T	p.Ile777Leu	missense_variant	16/21	1		ENSP00000267229.7
RBM26	ENST00000622611.4	c.2416A>T	p.Ile806Leu	missense_variant	17/22	2		ENSP00000483408.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 05, 2024

The c.2329A>T (p.I777L) alteration is located in exon 16 (coding exon 16) of the RBM26 gene. This alteration results from a A to T substitution at nucleotide position 2329, causing the isoleucine (I) at amino acid position 777 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.97
DEOGEN2	Benign	0.017	.;.;.;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Benign	0.0067	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.46	.;.;.;N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.52	N;.;N;.
REVEL	Benign	0.11
Sift	Benign	0.37	T;.;T;.
Sift4G	Benign	0.58	T;T;T;T
Polyphen		0.032	B;.;B;B
Vest4		0.17
MutPred		0.17		.;.;.;Loss of methylation at K802 (P = 0.0558);
MVP		0.25
MPC		0.46
ClinPred		0.63	D
GERP RS		4.0
Varity_R		0.079
gMVP		0.086

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-79916816;